Clinical description, molecular delineation and genotype–phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients

Medientyp: E-Artikel
Titel: Clinical description, molecular delineation and genotype–phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients
Beteiligte: Martinez-Cayuelas, Elena; Blanco-Kelly, Fiona; Lopez-Grondona, Fermina; Swafiri, Saoud Tahsin; Lopez-Rodriguez, Rosario; Losada-Del Pozo, Rebeca; Mahillo-Fernandez, Ignacio; Moreno, Beatriz; Rodrigo-Moreno, Maria; Casas-Alba, Didac; Lopez-Gonzalez, Aitor; García-Miñaúr, Sixto; Ángeles Mori, Maria; Pacio-Minguez, Marta; Rikeros-Orozco, Emi; Santos-Simarro, Fernando; Cruz-Rojo, Jaime; Quesada-Espinosa, Juan Francisco; Sanchez-Calvin, Maria Teresa; Sanchez-del Pozo, Jaime; Bernado Fonz, Raquel; Isidoro-Garcia, Maria; Ruiz-Ayucar, Irene; Alvarez-Mora, Maria Isabel; [...]
Erschienen: BMJ, 2023
Erschienen in: Journal of Medical Genetics, 60 (2023) 7, Seite 644-654
Sprache: Englisch
DOI: 10.1136/jmg-2022-108632
ISSN: 0022-2593; 1468-6244
Entstehung:
Anmerkungen:
Beschreibung: <jats:sec><jats:title>Background</jats:title><jats:p>KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving<jats:italic>ANKRD11</jats:italic>cause KBG syndrome, but no genotype–phenotype correlation has been reported.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire. Manifestations present in >50% of the patients and a ‘phenotypical score’ were used to perform a genotype–phenotype correlation in 340 patients from our cohort and the literature.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Neurodevelopmental delay, macrodontia, triangular face, characteristic ears, nose and eyebrows were the most prevalentf (eatures. 82.8% of the patients had at least one of seven main comorbidities: hearing loss and/or otitis media, visual problems, cryptorchidism, cardiopathy, feeding difficulties and/or seizures. Associations found included a higher phenotypical score in patients with sequence variants compared with CNVs and a higher frequency of triangular face (71.1% vs 42.5% in CNVs). Short stature was more frequent in patients with exon 9 variants (62.5% inside vs 27.8% outside exon 9), and the prevalence of intellectual disability/attention deficit hyperactivity disorder/autism spectrum disorder was lower in patients with the c.1903_1907del variant (70.4% vs 89.4% other variants). Presence of macrodontia and comorbidities were associated with larger deletion sizes and hand anomalies with smaller deletions.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We present a detailed phenotypical description of KBG syndrome in the largest series reported to date of 67 patients, provide evidence of a genotype–phenotype correlation between some KBG features and specific<jats:italic>ANKRD11</jats:italic>variants in 340 patients, and propose updated clinical diagnostic criteria based on our findings.</jats:p></jats:sec>

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: